The Aerosol Biology/Small Animal Models Core, hereafter referred to as the ABSAM Core or Core, will provide support for smallpox and pneumonic plague research as these diseases will be the most intensely studied NIAID Category A agents in Region 7. Other in vivo pathogen models wil be developed with the judicious selection of consultants, and as the needs arise Although the Core will be capable of infecting animals through a full range of inoculation routes, it will provide exceptional support for the use of respiratory routes of infection. The respiratory tract is the route of infection of the majority of human pathogens and will likely be the target of bioweapons; however, there Is a paucity of information in the scientific literature describing the molecular pathogenesis of NIAID category A, B, and C agents following respiratory tract infections, and the innate and mucosal responses to such infections. The starting point for the study of interactions of pathogens with the respiratory tract is a reproducible and efficient method for mimicking the natural infection. The Core will have expertise to infect animals by the intranasal, intratracheal, and aerosol exposure routes of inoculation. A major focus of the Core will be to provide support for the generation and quantification of aerosols with a wide range of mean aerodynamic particle sizes permitting the delivery of both bacteria and viruses to distinct regions of the respiratory tract. Existing and custom designed instrumentation will be used to support the study of basic questions in pathogenesis following aerosol infection, and to develop specific challenge models for preclinical testing of therapeutics and prophylactics for NIAID category A, B. and C agents. The Core will have the capacity to aerosolize and deliver therapeutics to the respiratory tract for the study of early intervention strategies, and will develop and test instrumentation designed to inactivate bioparticles in the air. Additional Core services will include: animal acquisition, quarantine and acclimation, health surveillance, husbandry, specimen collection, surgical services, clinical laboratory sample analysis, pathology services, and report writing. The Core will support studies in Region 7, at other Centers in the RCE network, and those originating from qualified biotechnology companies. Small biotechnology companies may find this Core particularly attractive as they will likely lack BSL-3 facilities, and the required regulatory oversight for using animals in biomedical research (AAALAC, USDA, and PHS). In addition, these companies will typically lack the expertise to carry out in vivo infections, to provide animal husbandry for infected animals, and to perform techniques necessary to acquire specimens for determination of experimental end-points.